1-acetyl-6-bromo-5-methoxyindoline | 256923-98-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-acetyl-6-bromo-5-methoxyindoline
• 英文别名: 1-(6-bromo-5-methoxy-2,3-dihydroindol-1-yl)ethanone
• CAS: 256923-98-5
• 化学式: C₁₁H₁₂BrNO₂
• 分子量: 270.126
• InChiKey: OCEAQMQNNWWZRH-UHFFFAOYSA-N

物化性质

• 沸点：
  465.8±45.0 °C(Predicted)
• 密度：
  1.492±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-acetyl-6-bromo-5-methoxyindoline 在 盐酸 、 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 1,4-二氧六环 为溶剂， 生成 5-Methoxy-6-((3R,5S)-3,4,5-trimethyl-piperazin-1-yl)-2,3-dihydro-1H-indole
  参考文献：
  名称：

  Identification of a potent and selective 5-HT1B receptor antagonist

  摘要：

  An SAR study around the mixed 5-HT1ABD receptor antagonist SB-272183 found that introduction of cis-2,6-dimethyl substitution onto the piperazine ring was a key structural change, which imparted a combination of both excellent selectivity over the 5-HT1A and 5-HT1D receptors and low intrinsic activity. This led to the identification of the selective 5-HT1B receptor antagonist SB-616234. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.085
• 作为产物：
  描述：

  N-乙酰基吲哚啉 在 过氧乙酸 、 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 三氯化铝 、 potassium carbonate 、 溶剂黄146 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-acetyl-6-bromo-5-methoxyindoline
  参考文献：
  名称：

  Identification of a potent and selective 5-HT1B receptor antagonist

  摘要：

  An SAR study around the mixed 5-HT1ABD receptor antagonist SB-272183 found that introduction of cis-2,6-dimethyl substitution onto the piperazine ring was a key structural change, which imparted a combination of both excellent selectivity over the 5-HT1A and 5-HT1D receptors and low intrinsic activity. This led to the identification of the selective 5-HT1B receptor antagonist SB-616234. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.085

文献信息

• Novel and Selective 5-HT_2C/2B Receptor Antagonists as Potential Anxiolytic Agents:  Synthesis, Quantitative Structure−Activity Relationships, and Molecular Modeling of Substituted 1-(3-Pyridylcarbamoyl)indolines
  作者：Steven M. Bromidge、Steven Dabbs、David T. Davies、D. Malcolm Duckworth、Ian T. Forbes、Peter Ham、Graham E. Jones、Frank D. King、Damian V. Saunders、Susannah Starr、Kevin M. Thewlis、Paul A. Wyman、Frank E. Blaney、Christopher B. Naylor、Fiona Bailey、Thomas P. Blackburn、Vicky Holland、Guy A. Kennett、Graham J. Riley、Martyn D. Wood

  DOI：10.1021/jm970741j

  日期：1998.5.1

  The synthesis, biological activity, and molecular modeling of a novel series of substituted 1-(3-pyridylcarbamoyl)indolines are reported. These compounds are isosteres of the previously published indole urea 1 (SB-206553) and illustrate the use of aromatic disubstitution as a replacement for fused five-membered rings in the context of 5-HT2C/2B receptor antagonists. By targeting a region of space previously

  报道了一系列新的取代的1-（3-吡啶基氨基甲酰基）二氢吲哚的合成，生物活性和分子模型。这些化合物是先前公开的吲哚脲1（SB-206553）的等排体，并说明了在5-HT2C / 2B受体拮抗剂的背景下使用芳香族脱位取代稠合的五元环。通过靶向先前鉴定为在5-HT2C受体上空间允许但在5-HT2A受体上不允许的空间区域，我们已经鉴定出许多化合物，它们是迄今报道的最有效和选择性最强的5-HT2C / 2B受体拮抗剂。根据其整体生物学特征选择了46（SB-221284）作为新的潜在非镇静抗焦虑药进行进一步评估。
• [EN] PIPERAZINE DERIVATIVES AS 5-HT1B ANTAGONISTS<br/>[FR] DERIVES DE PIPERAZINE UTILISES EN TANT QU'ANTAGONISTES DE 5-HT1B
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2001023374A1

  公开（公告）日：2001-04-05

  Piperazine derivatives of formula (I) processes for their preparation, pharmaceutical compositions containing them and to their use in therapy as 5-HT1B antagonists. W,Y,Ra-Reare so defined in the application.

  式(I)的哌嗪衍生物，其制备方法，包含它们的制药组合物以及作为5-HT1B拮抗剂在治疗中的用途。W，Y，Ra-Re在申请中有定义。
• Piperazine derivatives their preparation and uses in therapy
  申请人：——

  公开号：US20040142925A1

  公开（公告）日：2004-07-22

  Compounds of formula (I) or a pharmaceutically acceptable salt thereof are disclosed: 1 in which R a is a group of formula (i) 2 wherein P 2 is phenyl, naphthyl, heteroaryl or a 5 to 7 membered heterocyclic ring; P 3 is phenyl, naphthyl or heteroaryl; R 1 is NR 4 COR 5 , NR 4 SO 2 R 5 , CH 2 NR 4 SO 2 R 5 , CH 2 NR 4 COR 5 or CH 2 NR 4 CO 2 R 5 where R 4 and R 5 are independently hydrogen or C 1-6 alkyl; R 2 and R 3 are independently halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, COC 1-6 alkyl, haloC 1-6 alkyl, cyano or NR 6 R 7 where R 6 and R 7 are independently hydrogen or C 1-6 alkyl; b and c are independently 0, 1, 2 or 3; Y is a single bond, CH 2 or NH; W is —(CR 9 R 10 ) t - where t is 2, 3 or 4 and R 9 and R 10 are independently hydrogen or C 1-6 alkyl or W is a group CH═CH; R b is hydrogen, halogen, C 1-6 alkyl, haloC 1-6 alkyl, COC 1-6 alkyl, cyano or C 1-6 alkoxy; and R c is hydrogen or C 1-6 alkyl. Processes for preparation of the compounds and their uses in therapy, particularly depression, are also disclosed.

  揭示了式（I）的化合物或其药学上可接受的盐：其中，R是式（i）的基团，式中P2是苯基、萘基、杂环芳基或5至7成员杂环环；P3是苯基、萘基或杂环芳基；R1是NR4COR5、NR4SO2R5、CH2NR4SO2R5、CH2NR4COR5或CH2NR4CO2R5，其中R4和R5独立地为氢或C1-6烷基；R2和R3独立地为卤素、C1-6烷基、C3-6环烷基、C1-6烷氧基、COC1-6烷基、卤基C1-6烷基、氰基或NR6R7，其中R6和R7独立地为氢或C1-6烷基；b和c独立地为0、1、2或3；Y为单键、CH2或NH；W为—（CR9R10）t-，其中t为2、3或4，且R9和R10独立地为氢或C1-6烷基，或W为基团CH═CH；Rb为氢、卤素、C1-6烷基、卤基C1-6烷基、COC1-6烷基、氰基或C1-6烷氧基；Rc为氢或C1-6烷基。还揭示了制备这些化合物的方法以及它们在治疗中的用途，特别是抑郁症。
• Piperazine derivatives as 5-HT1B antagonists
  申请人：SmithKline Beecham p.I.c.

  公开号：US20040176388A1

  公开（公告）日：2004-09-09

  Piperazine derivatives of formula (I) processes for their preparation, pharmaceutical compositions containing them and to their use in therapy as 5-HT 1B antagonists. W,Y,R a -R e are so defined in the application. 1

  公式(I)的吡哆醇衍生物，其制备方法，包含它们的制药组合物以及它们作为5-HT1B拮抗剂在治疗中的应用。其中，W，Y，Ra-Re在申请中有定义。
• Piperazine derivatives, their preparation and uses in therapy
  申请人：SmithKline Beecham plc

  公开号：US07109201B2

  公开（公告）日：2006-09-19

  Compounds of formula (I) or a pharmaceutically acceptable salt thereof are disclosed: in which Ra is a group of formula (i) wherein P2 is phenyl, naphthyl, heteroaryl or a 5 to 7 membered heterocyclic ring; P3 is phenyl, naphthyl or heteroaryl; R1 is NR4COR5, NR4SO2R5, CH2NR4SO2R5, CH2NR4COR5 or CH2NR4CO2R5 where R4 and R5 are independently hydrogen or C1-6alkyl; R2 and R3 are independently halogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy, COC1-6alkyl, haloC1-6alkyl, cyano or NR6R7 where R6 and R7 are independently hydrogen or C1-6alkyl; b and c are independently 0, 1, 2 or 3; Y is a single bond, CH2 or NH; W is —(CR9R10)t—where t is 2, 3 or 4 and R9 and R10 are independently hydrogen or C1-6alkyl or W is a group CH═CH; Rb is hydrogen, halogen, C1-6alkyl, haloC1-6alkyl, COC1-6alkyl, cyano or C1-6alkoxy; and Rc is hydrogen or C1-6alkyl. Processes for preparation of the compounds and their uses in therapy, particularly depression, are also disclosed.

  公开了式（I）的化合物或其药学上可接受的盐：其中Ra是式（i）的基团，其中P2是苯基，萘基，杂环芳基或5到7成员杂环环；P3是苯基，萘基或杂环芳基；R1是NR4COR5，NR4SO2R5，CH2NR4SO2R5，CH2NR4COR5或CH2NR4CO2R5，其中R4和R5独立地是氢或C1-6烷基；R2和R3独立地是卤素，C1-6烷基，C3-6环烷基，C1-6烷氧基，COC1-6烷基，卤基C1-6烷基，氰基或NR6R7，其中R6和R7独立地是氢或C1-6烷基；b和c独立地为0、1、2或3；Y是单键，CH2或NH；W是—（CR9R10）t—，其中t为2、3或4，R9和R10独立地是氢或C1-6烷基，或W是基团CH═CH；Rb是氢，卤素，C1-6烷基，卤基C1-6烷基，COC1-6烷基，氰基或C1-6烷氧基；Rc是氢或C1-6烷基。还公开了制备这些化合物的方法以及它们在治疗中的用途，特别是抑郁症。